J19140: A pilot study of a DNAJB1-PRKACA fusion kinase peptide vaccine combined with nivolumab and ipilimumab for patients with fibrolamellar hepatocellular carcinoma
Johns Hopkins Kimmel Cancer Center in Baltimore
The purpose of this research study is to determine the safety and also the immune effects of the DNAJB1-PRKACA fusion kinase peptide vaccine (FLC peptide vaccine) given in combination with nivolumab and ipilimumab in patients with fibrolamellar hepatocellular carcinoma (FLC).
Patients must be 12 years of age or older. Patients less than 18 are eligible to enroll only after 6 adult patients have been enrolled in the study. Patients must have an ECOG performance status of 0-1 as determined by the study team. Patients must have FLC that is metastatic or unresectable and must have the presence of the DNAJB1-PRKACA fusion transcript as assessed by RNA-sequencing in archival tissue. Patients who are candidates for potentially curative interventions, including but not limited to surgical resection, radiofrequency ablation, or liver transplantation, are not eligible. NO chemotherapy, biological cancer therapy, or radiation within 14 days prior to first dose of study drug. NO surgery within 28 days of dosing of study drug. NO history of severe hypersensitivity reaction to any monoclonal antibody. NO history of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4, or anti-LAG-3 antibodies. NO autoimmune disease that has required systematic treatment in the past 2 years. NO diagnosed immunodeficiency. NO history of HIV/AIDS, hepatitis B, or hepatitis C. NO uncontrolled intercurrent illness. NO clinically meaningful ascites. Patients must be willing and able to follow the study schedule. Other inclusion/exclusion criteria as specified per protocol.
Treatment will be administered on an outpatient basis. During cycle 1 (cycle equal to 3 weeks) patiens 1-3 will receive the FLC peptide vaccine alone once a week. During cycles 2-5 (cycle equal to 3 weeks) patients 1-3 will receive the FLC peptide vaccine in combination with nivolumab and ipilimumab every 3 weeks. From cycle 6 (cycle equal to 4 weeks) and beyond patients 1-3 will receive nivolumab every 4 weeks and the FLC peptide vaccine every 12 weeks. During cycle 1 (cycle equal to 3 weeks) patients 4-12 will receive the FLC peptide vaccine in combination with nivolumab and ipilimimab on day 1, then the FLC vaccine alone once a week. During cycles 2-4 (cycle equal to 3 weeks) patients 4-12 will receive the FLC peptide vaccine in combination with nivolumab and ipilimumab once a week. From cycle 5 and beyond (cycle equal to 4 weeks) patients 4-12 will receive nivolumab every 4 weeks and the FLC peptide vaccine every 12 weeks.
08/07/2020 05:02 AM